Ion trap array for high throughput charge detection mass spectrometry

Abstract

An electrostatic linear ion trap (ELIT) array includes multiple elongated charge detection cylinders arranged end-to-end and each defining an axial passageway extending centrally therethrough, a plurality of ion mirror structures each defining a pair of axially aligned cavities and an axial passageway extending centrally therethrough, wherein a different ion mirror structure is disposed between opposing ends of each cylinder, and front and rear ion mirrors each defining at least one cavity and an axial passageway extending centrally therethrough, the front ion mirror positioned at one end of the arrangement of charge detection cylinders and the rear ion mirror positioned at an opposite end of the arrangement of charge detection cylinders, wherein the axial passageways of the charge detection cylinders, the ion mirror structures, the front ion mirror and the rear ion mirror are coaxial to define a longitudinal axis passing centrally through the ELIT array. In a second aspect, an ELIT array comprises a plurality of non-coaxial ELIT regions, wherein ions are selectively guided into each of the ELIT regions.

What is claimed is: 
     
       1. An electrostatic linear ion trap (ELIT) array, comprising:
 a plurality of elongated charge detection cylinders arranged end-to-end and each defining an axial passageway extending centrally therethrough, 
 a plurality of ion mirror structures each defining a pair of axially aligned cavities and each defining an axial passageway therethrough extending centrally through both cavities, wherein a different one of the plurality of ion mirror structures is disposed between opposing ends of each arranged pair of the elongated detection cylinders, and 
 front and rear ion mirrors each defining at least one cavity and an axial passageway extending centrally therethrough, the front ion mirror positioned at one end of the plurality of charge detection cylinders and the rear ion mirror positioned at an opposite end of the plurality of charge detection cylinders, 
 wherein the axial passageways of the plurality of charge detection cylinders, the plurality of ion mirror structures, the front ion mirror and the rear ion mirror are axially aligned with one another to define a longitudinal axis passing centrally through the ELIT array. 
 
     
     
       2. The ELIT array of  claim 1 , wherein each of the plurality of ion mirror structures comprise a single ion mirror defining a single cavity, a first aperture at one end of the ion mirror open to the single cavity, a second aperture at an opposite end of the ion mirror and open to the single cavity, and a plate or ring positioned centrally with the single cavity and axially bisecting the single cavity into the pair of axially aligned cavities, the plate or ring defining a third aperture therethrough and open to both of the axially aligned cavities,
 and wherein the longitudinal axis of the ELIT array extends centrally through first aperture, the second aperture, third aperture and the pair of axially aligned cavities of each of the plurality of ion mirror structures. 
 
     
     
       3. The ELIT array of any of  claim 1 , wherein the front ion mirror defines a single cavity, a first aperture at one end of the front ion mirror open to the single cavity of the front ion mirror and a second aperture at an opposite end of the front ion mirror and open to the single cavity of the front ion mirror,
 and wherein the longitudinal axis of the ELIT array extends centrally through the first and second apertures and through the single cavity of the front ion mirror, 
 and wherein the first aperture of the front ion mirror defines an ion inlet to the ELIT array and the second aperture of the front ion mirror is positioned opposite to an exposed end of the one of the plurality of charge detection cylinders at the one end of the plurality of charge detection cylinders. 
 
     
     
       4. The ELIT array of  claim 1 , wherein the rear ion mirror defines a single cavity, a first aperture at one end of the rear ion mirror open to the single cavity of the rear ion mirror and a second aperture at an opposite end of the rear ion mirror and open to the single cavity of the rear ion mirror,
 and wherein the longitudinal axis of the ELIT array extends centrally through first and second apertures and through single cavity of the rear ion mirror, 
 and wherein the first aperture of the rear ion mirror is positioned opposite to an exposed end of the one of the plurality of charge detection cylinders at the opposite end of the plurality of charge detection cylinders and the second aperture of the rear ion mirror defines an ion outlet of the ELIT array. 
 
     
     
       5. The ELIT array of  claim 1 , further comprising at least one voltage source operatively coupled to each of the front ion mirror, the rear ion mirror and the plurality of ion mirror structures and configured to produce voltages for selectively establishing an ion transmission electric field or an ion reflection electric field therein, the ion transmission electric field configured to focus an ion passing through a respective one of the front ion mirror, the rear ion mirror and the plurality of ion mirror structures toward the longitudinal axis and the ion reflection electric field configured to cause an ion entering a respective one of the front ion mirror, the rear ion mirror and the plurality of ion mirror structures from a respective one of the plurality of charge detection cylinders to stop and accelerate in an opposite direction back through the respective one of the plurality of charge detection cylinders while also focusing the ion toward the longitudinal axis. 
     
     
       6. The ELIT array of  claim 5 , further comprising:
 a processor operatively coupled to the at least one voltage source, and 
 a memory having instructions stored therein which, when executed by the processor, cause the processor to control the at least one voltage source to establish an ion transmission field with the cavities of each of the front ion mirror, the rear ion mirror and the plurality of ion mirror structures such that ions entering the front ion mirror pass through each of the front ion mirror, the rear ion mirror, each of the plurality of ion mirror structures and each of the plurality of charge detection cylinders and exit the ELIT array. 
 
     
     
       7. The ELIT array of  claim 6 , wherein the instructions stored in the memory further include instructions which, when executed by the processor, cause the processor to control the at least one voltage source to establish the ion reflection field with the at least one cavity of the rear ion mirror while maintaining the ion transmission electric field in the cavities of the front ion mirror and the plurality of ion mirror structures. 
     
     
       8. The ELIT array of  claim 7 , wherein the ELIT defines a plurality of axially aligned ELIT regions each including a different one of the plurality of charge detection cylinders and cavities of respective ones of the front ion mirror, the rear ion mirror and the plurality of ion mirror structures positioned at opposite ends thereof,
 and wherein the instructions stored in the memory further include instructions which, when executed by the processor, cause the processor to control the at least one voltage source to sequentially establish the ion reflection field with the cavities each of the plurality of ion mirror structures, beginning with the one of the plurality of ion mirror structures positioned at the opposite end of the one of the plurality of cylinders disposed between the rear ion mirror and the one of the plurality of ion mirror structures, while maintaining the ion transmission electric field in the cavities of the front ion mirror and each of the remaining plurality of ion mirror structures, followed by controlling the at least one voltage source to establish the ion reflection field with the at least one cavity of the front ion mirror, in a manner which successively traps a different one of the ions entering the front ion mirror in each of the plurality of ELIT regions such that an ion trapped within each of the plurality of ELIT regions oscillates back and forth between the cavities of the respective ones of the front ion mirror, the rear ion mirror and the plurality of ion mirror structures each time passing through a respective one of the plurality of charge detection cylinders. 
 
     
     
       9. The ELIT array of  claim 8 , further comprising a plurality of charge preamplifiers each having an input operatively coupled to a different one of the plurality of charge detection cylinders and each having an output operatively coupled to the processor, each of the plurality of charge preamplifiers configured to produce charge detection signals upon detection of a charge induced on the respective one of the plurality of charge detection cylinders as a respective ion passes therethrough,
 and wherein the instructions stored in the memory further include instructions which, when executed by the processor, cause the processor to record the charge detection signals produced by each of the plurality of charge preamplifiers. 
 
     
     
       10. The ELIT array of  claim 9 , wherein the instructions stored in the memory further include instructions which, when executed by the processor, cause the processor to control the at least one voltage source to trap one of the ions entering the front ion mirror in any of the plurality of ELIT regions by controlling the at least one voltage source to establish the ion reflection electric field in the cavity of a corresponding upstream one of the front ion mirror and the plurality of ion mirror structures upon detection of a charge detection signal produced by a respective one of the plurality of charge preamplifiers. 
     
     
       11. The ELIT array of  claim 9 , wherein the instructions stored in the memory further include instructions which, when executed by the processor, cause the processor to determine a respective ion charge and at least one of an ion mass-to-charge ratio and an ion mass based on the recorded charge detection signals produced by each of the plurality of charge preamplifiers. 
     
     
       12. The ELIT array of  claim 8 , wherein the instructions stored in the memory further include instructions which, when executed by the processor, cause the processor to control the at least one voltage source to trap one of the ions entering the front ion mirror in any of the plurality of ELIT regions by controlling the at least one voltage source to establish the ion reflection electric field in the cavity of a corresponding upstream one of the front ion mirror and the plurality of ion mirror structures after a time delay has elapsed since controlling the at least one voltage source to establish the ion reflection electric field in the cavity of a corresponding downstream one of the rear ion mirror and the plurality of ion mirror structures. 
     
     
       13. A charge detection mass spectrometer (CDMS), comprising:
 a source of ions configured to generate and supply ions, 
 an electrostatic linear ion trap (ELIT) array of  claim 8 , the ELIT array configured to receive at least some of the ions supplied by the source of ions, and 
 means for controlling each of the plurality of ion mirrors to trap a different one of the ions supplied by the source of ions in each of the plurality of ELIT regions and to cause the ion trapped in each of the plurality of ELIT regions to oscillate back and forth between the respective pair of the plurality of ion mirrors each time passing through a respective one of the plurality of charge detection cylinders. 
 
     
     
       14. The CDMS of  claim 13 , wherein the ELIT regions are arranged in line with one another such that the axial passageways of the plurality of ion mirrors and the axial passageways of the plurality of charge detection cylinders are coaxial and such that a longitudinal axis extending through the ELIT array extends centrally through each of the passageways of each of the plurality of ion mirrors and each of the plurality of charge detection cylinders,
 and wherein the means for controlling each of the plurality of ion mirrors includes means for guiding the ions supplied by the source of ions into and through the axially aligned passageways of each of the plurality of ELIT regions of the ELIT. 
 
     
     
       15. The CDMS of  claim 13 , wherein the axial passageways of at least one of the plurality of ELIT regions are not aligned with the axial passageways of at least another of the plurality of ELIT regions,
 and further comprising means for selectively guiding ions supplied by the ion source into each of the ELIT regions. 
 
     
     
       16. The CDMS of  claim 13 , further comprising:
 a plurality of charge preamplifiers each having an input coupled to a respective one of the plurality of charge detection cylinders and an output, each of the plurality of charge preamplifiers configured to produce a charge detection signal at the output thereof upon detection at the respective input of a charge induced on the respective one of the plurality of charge detection cylinders resulting from passage of an ion axially therethrough, 
 a processor operatively coupled to the output of each of the plurality of charge preamplifiers, and 
 a memory having instructions stored therein which, when executed by the processor, cause the processor to monitor the outputs of the plurality of charge preamplifiers and to record in the memory a plurality of sets of charge detection signals each containing recorded charge detection signals produced by a different one of the plurality of charge preamplifiers, 
 wherein the instructions stored in the memory include instructions which, when executed by the processor, cause the processor to process the plurality of sets of recorded charge detection signals to determine a corresponding plurality of ion charge values and associated ion mass-to-charge ratio or mass values. 
 
     
     
       17. A system for separating ions comprising:
 an ion source configured to generate ions from a sample, 
 at least one ion separation instrument configured to separate the generated ions as a function of at least one molecular characteristic, and 
 the ELIT array of  claim 1 , wherein ions exiting the at least one ion separation instrument pass into the ELIT array via the front ion mirror. 
 
     
     
       18. A system for separating ions comprising:
 an ion source configured to generate ions from a sample, 
 a first mass spectrometer configured to separate the generated ions as a function of mass-to-charge ratio, 
 an ion dissociation stage positioned to receive ions exiting the first mass spectrometer and configured to dissociate ions exiting the first mass spectrometer, 
 a second mass spectrometer configured to separate dissociated ions exiting the ion dissociation stage as a function of mass-to-charge ratio, and 
 a charge detection mass spectrometer (CDMS), including the ELIT array of  claim 1 , coupled in parallel with and to the ion dissociation stage such that the CDMS can receive ions exiting either of the first mass spectrometer and the ion dissociation stage, 
 wherein masses of precursor ions exiting the first mass spectrometer are measured using the CDMS, mass-to-charge ratios of dissociated ions of precursor ions having mass values below a threshold mass are measured using the second mass spectrometer, and mass-to-charge ratios and charge values of dissociated ions of precursor ions having mass values at or above the threshold mass are measured using the CDMS. 
 
     
     
       19. A method of measuring ions supplied to an ion inlet of an electrostatic linear ion trap (ELIT) array having a plurality of ion mirrors and a plurality of elongated charge detection cylinders each defining a respective axial passageway therethrough, wherein the plurality of charge detection cylinders are arranged end-to-end in cascaded relationship with a different one of the plurality of ion mirrors positioned between each arranged pair of the elongated charge detection cylinders and with first and last ones of the plurality of ion mirrors positioned at respective opposite ends of the cascaded arrangement, wherein the first and last ion mirrors define the ion inlet and an ion exit of the ELIT array respectively, and wherein the axial passageways of each of the plurality of ion mirrors and charge detection cylinders are collinear with one another and define a longitudinal axis centrally therethrough to form a sequence of axially aligned ELIT regions each defined by a combination of one of the plurality of charge detection cylinders and a respective pair of the plurality of ion mirrors at each end thereof, the method comprising:
 controlling at least one voltage source to apply voltages to each of the plurality of ion mirrors to establish an ion transmission electric field therein to pass the ions entering the ion inlet of the ELIT through each of the plurality of ion mirrors and charge detection cylinders and the ion exit of the ELIT array, wherein each ion transmission field is configured to focus ions passing therethrough toward the longitudinal axis, and 
 controlling the at least one voltage source to sequentially modify the voltages applied to each the plurality of ion mirrors while maintaining previously applied voltages to remaining ones of the plurality of ion mirrors, beginning with the last ion mirror and ending with the first ion mirror, to sequentially establish an ion reflection electric field in each of the plurality of ion mirrors in a manner that sequentially traps a different ion in each of the ELIT regions, wherein each ion reflection electric field is configured to cause an ion entering a respective ion mirror from an adjacent one of the plurality of charge detection cylinders to stop and accelerate in an opposite direction back through the respective one of the plurality of charge detection cylinders, 
 wherein the ion trapped in each respective ELIT region oscillates back and forth between the respective ones of the plurality of ion mirrors, under the influence of the ion reflection electric fields established therein, each time passing through a respective one of the plurality of charge detection cylinders and inducing a corresponding charge thereon, 
 detecting the charge induced on each of the plurality of charge detection cylinders by a respective trapped ion with each pass therethrough, and 
 recording in a memory the charges induced on each of the plurality of charge detection cylinders by a respective trapped ion over a duration of a respective charge measurement event, wherein each charge measurement event has a duration defined by one of a passage of a predefined period of time and a predefined number of passes of the respective ion through the respective charge detection cylinder. 
 
     
     
       20. The method of  claim 19 , further comprising determining an ion charge and at least one of an ion mass-to-charge ratio and an ion mass based on the recorded charges for each of the ELIT regions.